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Vitamin B12: An Essential Nutrient for Good Health
May 04, 2022
Vitamin B12, also referred to as cobalamin, is a water-soluble B vitamin that is essential to overall health. Vitamin B12 can be in the form of cyanocobalamin (free form), or in the coenzyme form as methylcobalamin or deoxyadenosylcobalamin. Both methylcobalamin and deoxyadenosylcobalamin are metabolically active forms of vitamin B12. Cyanocobalamin becomes biologically active after being converted to methylcobalamin or 5-deoxyadenosylcobalamin in the body.1
Vitamin B12 is naturally found in some foods where it is bound to protein, however the body requires it to be released before it is absorbed.2 This process begins in the mouth while chewing, and as free vitamin B12 is released, it combines with a protein called haptocorrin, found in saliva. As the food matrix reaches the stomach, more B12 is released by the action of hydrochloric acid in the stomach and the enzyme, gastric protease. It binds again to the cobalamin-binding protein, haptocorrin, until it reaches the small intestine. In the small intestine, pancreatic enzymes degrade haptocorrin, freeing vitamin B12 to bind to intrinsic factor, another binding protein that is secreted by the parietal cells in the stomach. It is ultimately absorbed in the distal ileum of the small intestine.1,2
Why is Vitamin B12 Important?
Vitamin B12 has numerous roles in the body, including being an important cofactor in protein and fat metabolism, assisting with normal nervous system function, and needed for production of hemoglobin for transporting oxygen to our cells.
Function of Cofactors
Vitamin B12 plays an essential role in energy production via the citric acid cycle and the coenzyme intermediate, succinyl-CoA. It is also essential for folate metabolism where methylcobalamin is required for the function of the folate-dependent enzyme, methionine synthase, to convert homocysteine to methionine. From here, methionine is required for the synthesis of S-adenosylmethionine (SAM-e), which is involved in a number of methylation reactions. (Figure 1).3 Adequate function of the enzyme, methionine synthase, is required to prevent an accumulation of homocysteine, an amino acid that has been associated with a negative impact on cardiovascular health.4
Figure 1: Vitamin B12 And Homocysteine Metabolism
Vitamin B12 is also required as a cofactor to produce succinyl CoA, for energy production in the citric cycle (Figure 2),3 as well as for the synthesis of hemoglobin, found in red blood cells to help carry oxygen in the body. The form of vitamin B12, 5-Deoxyadenosylcobalamin, is required for the conversion of L-methylmalonyl-coenzyme A to succinyl-coenzyme A (succinyl CoA).
Vitamin B12 also plays essential role as a coenzyme to support the health of the nervous system. The myelin sheath that surrounds and insulates the axons of nerves throughout the body requires vitamin B12 to maintain and support their integrity. Through this important contribution to myelin synthesis, protection and maintenance, vitamin B12 also assists with nerve regeneration when damage has occurred.4,5
How Much Vitamin B12 Do I Need?
While most adults in the U.S. have adequate vitamin B12 status, women, vegetarians and vegans, those of lower socioeconomic status and non-Hispanic Blacks are most likely to have sub-optimal intakes of vitamin B12.6 It is important to note that for those older than 60, nearly one in five have a vitamin B12 deficiency, suggesting that age may impact B12 nutrient status.7
The Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering and Medicine, determine the Dietary Reference Intakes (DRIs)1 which vary by age and gender and include: Recommended Dietary Allowance (RDA), Adequate Intake (AI), Estimated Average Requirement (EAR), and Tolerable Upper Intake Level (UL*).
RDA for Vitamin B12
Birth to 6 months**
*= The Tolerable Upper Intake Level, or UL, is defined as the highest level of daily intake that is likely to pose no adverse health effects in most individuals. A UL for vitamin B12 has not been established, which means insufficient data existed when establishing a value.
**= Adequate Intake
Food Sources of Vitamin B12
Vitamin B12 is naturally present in foods of animal origin such as meat, poultry, fish eggs, and dairy products.2 Some foods fortified with vitamin B12 such as fortified breakfast cereals and nutritional yeasts are highly bioavailable sources of vitamin B12.8,9
Note: Because of the risk vitamin B12 insufficiency/deficiency in older adults due to protein-bound B12 malabsorption in foods containing Vitamin B12, the Food and Nutrition Board recommends that adults over age 50 consume B12-fortified foods and take a vitamin B12 supplement.1
Amount per Serving (mcg)
Beef liver, cooked 3 oz
Clams, 3 oz
Mussels, 3 oz
Cereal, fortified, 8 oz
Tuna, cooked, 3 oz
Nutritional yeast, fortified, ¼ cup
8.3 – 24
Salmon, Atlantic, cooked 3 oz
Beef, ground, 85% lean, 3 oz
Milk, 2% milkfat, 1 cup
Who is at Risk For and What are Causes of Vitamin B12 Deficiency?
There are certain populations, as well as some conditions, that put some individuals at greater risk for a vitamin B12 deficiency.
1. Older Adults
Food-bound vitamin B12 malabsorption in the elderly is a major cause of vitamin B12 deficiency. One study showed that over 40% of older adults who reside in assisted living and/or long-term care facilities, particularly with atrophic gastritis, have serum vitamin B12 levels showing a deficiency.10,11 Those with food- bound vitamin B12 malabsorption have an impaired ability to absorb food or protein-bound vitamin B12, however, individuals with this condition can still absorb vitamin B12 in the free form (e.g. B12 supplements).12
2. Common health conditions associated with Vitamin B12 deficiency include:
This condition is found in approximately 15-25% of older adults with a vitamin B12 deficiency,13 and has been estimated to be present in about 2% of individuals over age 60.14 Pernicious anemia is an autoimmune condition affecting the gastric mucosa, causing gastric atrophy.1,15 It attacks the parietal cells in the stomach, destroys production of intrinsic factor and leads to malabsorption of vitamin B12. Without treatment, pernicious anemia causes vitamin B12 deficiency, even in the presence of adequate vitamin B12 intake.
This condition may affect 10-30% of people over age 60.16 It affects the parietal cells in the stomach and may also be caused by an infection of the bacteria, Helicobacter pylori (H. pylori).17 A loss of gastric function with atrophic gastritis can result in bacterial overgrowth in the small intestine, and therefore inhibit absorption of vitamin B12 from food.
Both vegetarians and vegans who consume very small amounts or no animal products (meat, eggs, dairy, etc.) at all, are at a higher risk for developing a vitamin B12 deficiency.18 Animal based foods are natural sources of this key vitamin. It is recommended for vegetarians and vegans to consume vitamin B12 fortified foods, nutritional yeast, as well as a vitamin B12 supplement.19
4. Megaloblastic Anemia
If a vitamin B12 deficiency results in impairment of the methionine synthase, the regeneration of tetrahydrofolate (THF) is inhibited and traps folate in a form that is not usable by the body. This results in symptoms of a folate deficiency, even if folate intake is adequate. Folate is required for synthesis of nucleic acids (e.g. DNA). This impairment of DNA synthesis affects the rapidly dividing cells of bone marrow and causes the production of large, immature red blood cells that cannot enter the bloodstream to deliver oxygen. The resulting condition is referred to as megaloblastic anemia.6 While folic acid supplementation can help with resolving the anemia, if vitamin B12 deficiency is the cause, the condition will persist even if the anemia is resolved. Therefore, the underlying cause of megaloblastic anemia should first be determined before supplementing with folic acid.20
Should I Have My Vitamin B12 Level Checked?
For adults over age 50, it’s important to proactively talk to a doctor or health care practitioner about individual vitamin B12 level through diagnostics, since there is a higher risk for low vitamin B12 status or a vitamin B12 deficiency with increasing age.
Should I Add a Dietary Supplement to My Daily Routine?
It’s important for patients to communicate with their healthcare professionals about any changes to their daily regimen including dietary supplements. Work together to understand personal nutrition needs as well as current dietary patterns to identify nutrient gaps. For those who are still unable to meet their nutrient needs from diet alone, it’s important to discuss the need to fill any potential nutrient gaps with dietary supplements, as a safe and effective way to ensure adequate intake of all essential nutrients.
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These materials are intended for educational purposes only.
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**Based on U.S. News & World Report – Pharmacy Times Survey, 2021
†These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and https://www.ncbi.nlm.nih.gov/books/NBK114310/.
Stabler, Vitamin B12. In: Marriott, BP et al. eds. Present Knowledge in Nutrition. 11 ed. Washington, DC: Elsevier;2020:257-71.
Adamo Nutritional factors and aging in demyelinating diseases. Genes Nutr. 2014;9(1):360.
Shane Folic acid, vitamin B-12, and vitamin B-6. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483-518.
Han S, et Trends in dietary nutrients by demographic characteristics and BMI among US adults, 2003-2016. Nutrients 2019;11:2617.
Hunt A, et Vitamin B12 deficiency. BMJ 2014;349:g5226.
Watanabe F, et Vitamin B₁₂-containing plant food sources for vegetarians. Nutrients 2014;6:1861-73.
Damayanti D, et al. Foods and supplements associated with vitamin B(12) biomarkers among vegetarian and non-vegetarian participants of the Adventist Health Study-2 (AHS-2) Calibration Nutrients 2018;10:722.
Wong Vitamin B12 deficiency in the elderly: Is it worth screening? Hong Kong Med J 2015;21:155-64.
Pfisterer KJ, et Vitamin B12 status in older adults living in Ontario long-term care homes: incidence of deficiency with supplementation as a protective factor. Appl Physiol Nutr Metab 2016;41:219-22.
Ho C, Kauwell GP, Bailey Practitioners’ guide to meeting the vitamin B-12 recommended dietary allowance for people aged 51 years and older. J Am Diet Assoc. 1999;99(6):725-727.
Cavalcoli F, et Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: A review. World J Gastroenterol 2017;23:563-72.
Carmel R. Megaloblastic anemias. Curr Opin Hematol. 1994;1(2):107-112.
Rojas Hernandez CM. Advances in mechanisms, diagnosis, and treatment of pernicious anemia. Discov Med 2015;19:159-68.
Baik HW and Russell Vitamin B12 deficiency in the elderly. Annu Rev Nutr. 1999;19:357-377.
Neumann WL, et Autoimmune atrophic gastritis-- pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013;10(9):529-541.
Pawlak R, et al. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: A review of Eur J Clin Nutr 2014;68:541-8.
Herbert Vitamin B-12. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:191-205.
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